Bibliographic details of the publications referred to by author in this specification are collected at the end of the description.
Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other country.
Natural product screening is a term applied to the screening of natural environments for bioactive molecules. Particularly sought after bioactive molecules are those having potential as useful therapeutic agents. Natural environments include plants, microorganisms, coral and marine animals. The search for potential therapeutic agents for the treatment of cancer and infection by pathogenic organisms remains an important focus.
The Euphorbiaceae family of plants covers a wide variety of plants including weeds of Euphorbia species. There have been a variety of inconclusive reports on the potential effects of the sap of these plants on a variety of conditions as well as promoting tumorigenesis and causing skin and ocular irritation.
The most intensively studied species of this group is Euphorbia pilulifera L (synonyms E. hirta L., E. capitata Lam.), whose common names include pill-bearing spurge, snakeweed, cat's hair, Queensland asthma weed and flowery-headed spurge. The plant is widely distributed in tropical countries, including India, and in Northern Australia, including Queensland.
A recent report describes selective cytotoxicity of a number of tiglilane diterpene esters from the latex of Euphorbia poisonii, a highly toxic plant found in Northern Nigeria, which is used as a garden pesticide. One of these compounds has a selective cytotoxicity for the human kidney carcinoma cell line A-498 more than 10,000 times greater than that of adriamycin (Fatope et al., 1996).
Euphorbia hirta plants and extracts thereof have been considered for a variety of purposes, including tumor therapy (EP 0 330 094), AIDS-related complex and AIDS (HU-208790) and increasing immunity and as an anti-fungoid agent for treatment of open wounds (DE-4102054).
Thus, while there are isolated reports of anti-cancer activity of various Euphorbia preparations (see Fatope et al., 1996; Oksuz et al., 1996), not only are the compounds present in at least one Euphorbia species reported to be carcinogenic (Evans and Osman, 1974; Stavric and Stolz, 1976; Hecker, 1970), but at least one species has a skin-irritant and tumor-promoting effect (Gundidz et al., 1993) and another species reduces EBV-specific cellular immunity in Burkitt's lymphoma (Imai, 1994).
In accordance with the present invention, the inventors have identified chemical agents and fractions comprising these agents which are useful in the treatment and prophylaxis of infection by pathogenic or potentially pathogenic entities, or entities capable of opportunistic infection in mammals, including humans and primates, non-mammalian animals and avian species.